Molecular Neuroendocrinology Research Group, Bristol Medical School: Translational Health Sciences, University of Bristol, Bristol, United Kingdom.
Laboratory of Molecular Neuroendocrinology, Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
Mol Cell Proteomics. 2023 May;22(5):100544. doi: 10.1016/j.mcpro.2023.100544. Epub 2023 Apr 6.
The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus, whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses to neuronal stimulation are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt. In particular, changes in the phosphoproteome in the cell body are involved in the reorganization of the cytoskeleton and in axonal terminals the regulation of synaptic and secretory processes. We have identified that prohormone precursors including vasopressin and oxytocin are phosphorylated in axonal terminals and are hyperphosphorylated following stimulation. By multiomic integration of transcriptome and proteomic data, we identify changes to proteins present in afferent inputs to this nucleus.
下丘脑大细胞神经元的细胞体密集排列在下丘脑视上核中，而其轴突投射到解剖上离散的垂体后叶。我们利用这种独特的解剖结构，研究了生理刺激下神经元细胞体和轴突末梢的蛋白质组和磷酸化蛋白质组的动态变化。我们发现，神经元刺激引起的蛋白质组和磷酸化蛋白质组的反应在体细胞和轴突神经元区室之间有很大的不同，这表明每个细胞区室都需要不同程度的适应。特别是，细胞体中磷酸化蛋白质组的变化涉及细胞骨架的重组，而在轴突末梢中则涉及突触和分泌过程的调节。我们已经确定，包括血管加压素和催产素在内的前激素前体在轴突末梢被磷酸化，并且在刺激后被过度磷酸化。通过转录组和蛋白质组数据的多组学整合，我们鉴定出了该核团传入输入中存在的蛋白质的变化。
